Optimizing analyte sensor calibration

ABSTRACT

Method and apparatus for optimizing analyte sensor calibration including receiving a current blood glucose measurement, retrieving a time information for an upcoming scheduled calibration event for calibrating an analyte sensor, determining temporal proximity between the current blood glucose measurement and the retrieved time information for the upcoming calibration event, initiating a calibration routine to calibrate the analyte sensor when the determined temporal proximity is within a predetermined time period, and overriding the upcoming scheduled calibration event using the current blood glucose measurement are provided.

RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 17/328,768, filed May 24, 2021, now allowed, which is acontinuation of U.S. patent application Ser. No. 17/097,022 filed Nov.13, 2020, now U.S. Pat. No. 11,013,439, which is a continuation of U.S.patent application Ser. No. 15/604,648 filed May 24, 2017, which is acontinuation of U.S. patent application Ser. No. 14/285,575 filed May22, 2014, now U.S. Pat. No. 9,662,056, which is a continuation of U.S.patent application Ser. No. 13/544,934 filed Jul. 9, 2012, now U.S. Pat.No. 8,744,547, which is a continuation of U.S. patent application Ser.No. 12/242,823 filed Sep. 30, 2008, now U.S. Pat. No. 8,219,173,entitled “Optimizing Analyte Sensor Calibration”, the disclosures ofeach of which are incorporated herein by reference for all purposes.

TECHNICAL FIELD

The present disclosure relates to analyte monitoring devices andsystems. More specifically, the present disclosure relates to optimizingcalibration of analyte sensors in analyte monitoring devices andsystems.

BACKGROUND

There are significant therapeutic advantages for continuously monitoringanalyte levels such as glucose levels of diabetic patients. Commerciallyavailable continuous glucose monitoring systems use analyte sensors thatdetect the glucose levels of the patients for a predetermined timeperiod. During this time period, the analyte sensor is generallyrequired to be periodically calibrated with a blood glucose measurementusing, for example, an in vitro blood glucose meter.

Calibration of an analyte sensor typically follows a calibrationschedule over the life of the analyte sensor, and are intended tomaintain the accuracy of the analyte sensor during its useful life. Eachcalibration routine requires analysis of data from the analyte sensor inconjunction with a reference value, such as from a finger prick testusing a lancing device in conjunction with a conventional blood glucosemeter. While other areas of the body may be used to perform the bloodglucose measurement, such measurement typically requires drawing a bloodsample from the patient and applying the blood sample to a blood glucosetest strip. This is often a painful experience, which must be performedperiodically based on the calibration schedule of the analyte sensor.

SUMMARY

In accordance with the various embodiments of the present disclosure,there are provided method and apparatus for receiving a current bloodglucose measurement, retrieving a time information for an upcomingscheduled calibration event for calibrating an analyte sensor,determining temporal proximity between the current blood glucosemeasurement and the retrieved time information for the upcomingcalibration event, and initiating a calibration routine to calibrate theanalyte sensor when the determined temporal proximity is within apredetermined time period.

In another aspect, method and apparatus include receiving a currentreference data associated with a monitored analyte level, determiningwhether a next scheduled calibration event for calibrating an analytesensor associated with the monitored analyte level is within apredetermined time period, validating one or more conditions associatedwith the calibration of the analyte sensor when the next scheduledcalibration event is determined to be within the predetermined timeperiod, and calibrating the analyte sensor based on the received currentreference data.

In still a further aspect, an apparatus includes one or more processors;and a memory operatively coupled to the one or more processors forstoring instructions which, when executed by the one or more processors,retrieves a time information for an upcoming scheduled calibration eventfor calibrating an analyte sensor when a current blood glucosemeasurement is received, determines a temporal proximity between thecurrent blood glucose measurement and the retrieved time information forthe upcoming calibration event, and initiates a calibration routine tocalibrate the analyte sensor when the determined temporal proximity iswithin a predetermined time period.

These and other objects, features and advantages of the presentdisclosure will become more fully apparent from the following detaileddescription of the embodiments, the appended claims and the accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram illustrating an overall system for practicingone or more embodiments of the present disclosure;

FIG. 2 is an example flowchart for optimizing analyte sensor calibrationin accordance with one embodiment of the present disclosure;

FIG. 3 is an example flowchart for optimizing analyte sensor calibrationin accordance with another embodiment of the present disclosure; and

FIG. 4 is an example flowchart for optimizing analyte sensor calibrationin accordance with yet another embodiment of the present disclosure.

DETAILED DESCRIPTION

Before the present disclosure is described, it is to be understood thatthis invention is not limited to particular embodiments described, assuch may, of course, vary. It is also to be understood that theterminology used herein is for the purpose of describing particularembodiments only, and is not intended to be limiting, since the scope ofthe present disclosure will be limited only by the appended claims.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range, is encompassed within the invention. The upper and lowerlimits of these smaller ranges may independently be included in thesmaller ranges as also encompassed within the invention, subject to anyspecifically excluded limit in the stated range. Where the stated rangeincludes one or both of the limits, ranges excluding either or both ofthose included limits are also included in the invention.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although any methods andmaterials similar or equivalent to those described herein can also beused in the practice or testing of the present disclosure, the preferredmethods and materials are now described. All publications mentionedherein are incorporated herein by reference to disclose and describe themethods and/or materials in connection with which the publications arecited.

It must be noted that as used herein and in the appended claims, thesingular forms “a”, “an”, and “the” include plural referents unless thecontext clearly dictates otherwise.

The publications discussed herein are provided solely for theirdisclosure prior to the filing date of the present application. Nothingherein is to be construed as an admission that the present disclosure isnot entitled to antedate such publication by virtue of prior invention.Further, the dates of publication provided may be different from theactual publication dates which may need to be independently confirmed.

As will be apparent to those of skill in the art upon reading thisdisclosure, each of the individual embodiments described and illustratedherein has discrete components and features which may be readilyseparated from or combined with the features of any of the other severalembodiments without departing from the scope or spirit of the presentdisclosure.

The figures shown herein are not necessarily drawn to scale, with somecomponents and features being exaggerated for clarity.

Generally, embodiments of the present disclosure relate to methods anddevices for detecting at least one analyte such as glucose in bodyfluid. In certain embodiments, the present disclosure relates to thecontinuous and/or automatic in vivo monitoring of the level of ananalyte using an analyte sensor.

Accordingly, embodiments include analyte monitoring devices and systemsthat include an analyte sensor—at least a portion of which ispositionable beneath the skin of the user-for the in vivo detection, ofan analyte, such as glucose, lactate, and the like, in a body fluid.Embodiments include wholly implantable analyte sensors and analytesensors in which only a portion of the sensor is positioned under theskin and a portion of the sensor resides above the skin, e.g., forcontact to a transmitter, receiver, transceiver, processor, etc. Thesensor may be, for example, subcutaneously positionable in a patient forthe continuous or periodic monitoring of a level of an analyte in apatient's interstitial fluid. For the purposes of this description,continuous monitoring and periodic monitoring will be usedinterchangeably, unless noted otherwise.

The analyte level may be correlated and/or converted to analyte levelsin blood or other fluids. In certain embodiments, an analyte sensor maybe positioned in contact with interstitial fluid to detect the level ofglucose, which detected glucose may be used to infer the glucose levelin the patient's bloodstream. Analyte sensors may be insertable into avein, artery, or other portion of the body containing fluid. Embodimentsof the analyte sensors of the subject invention may be configured formonitoring the level of the analyte over a time period which may rangefrom minutes, hours, days, weeks, or longer.

Of interest are analyte sensors, such as glucose sensors, that arecapable of in vivo detection of an analyte for about one hour or more,e.g., about a few hours or more, e.g., about a few days of more, e.g.,about three or more days, e.g., about five days or more, e.g., aboutseven days or more, e.g., about several weeks or at least one month.Future analyte levels may be predicted based on information obtained,e.g., the current analyte level at time to, the rate of change of theanalyte, etc. Predictive alarms may notify the user of predicted analytelevels that may be of concern prior in advance of the analyte levelreaching the future level. This enables the user an opportunity to takecorrective action.

As described in detail below, in accordance with the various embodimentsof the present disclosure, there are provided method, apparatus andsystem for optimizing analyte sensor calibration to minimize the numberof blood glucose measurements in conjunction with the sensor calibrationschedule while maintaining the integrity of sensor accuracy.

FIG. 1 shows a data monitoring and management system such as, forexample, an analyte (e.g., glucose) monitoring system 100 in accordancewith certain embodiments. Embodiments of the subject invention arefurther described primarily with respect to glucose monitoring devicesand systems, and methods of glucose detection, for convenience only andsuch description is in no way intended to limit the scope of theinvention. It is to be understood that the analyte monitoring system maybe configured to monitor a variety of analytes at the same time or atdifferent times.

Analytes that may be monitored include, but are not limited to, acetylcholine, amylase, bilirubin, cholesterol, chorionic gonadotropin,creatine kinase (e.g., CK-MB), creatine, DNA, fructosamine, glucose,glutamine, growth hormones, hormones, ketones, lactate, peroxide,prostate-specific antigen, prothrombin, RNA, thyroid stimulatinghormone, and troponin. The concentration of drugs, such as, for example,antibiotics (e.g., gentamicin, vancomycin, and the like), digitoxin,digoxin, drugs of abuse, theophylline, and warfarin, may also bemonitored. In those embodiments that monitor more than one analyte, theanalytes may be monitored at the same or different times.

The analyte monitoring system 100 in one embodiment includes a sensor101, a data processing unit 102 connectable to the sensor 101, and aprimary receiver unit 104 which is configured to communicate with thedata processing unit 102 via a communication link 103. In certainembodiments, the primary receiver unit 104 may be further configured totransmit data to a data processing terminal 105 to evaluate or otherwiseprocess or format data received by the primary receiver unit 104. Thedata processing terminal 105 may be configured to receive data directlyfrom the data processing unit 102 via a communication link which mayoptionally be configured for bi-directional communication. Further, thedata processing unit 102 may include a transmitter or a transceiver totransmit and/or receive data to and/or from the primary receiver unit104, the data processing terminal 105 or optionally the secondaryreceiver unit 106.

Also shown in FIG. 1 is an optional secondary receiver unit 106 which isoperatively coupled to the communication link and configured to receivedata transmitted from the data processing unit 102. The secondaryreceiver unit 106 may be configured to communicate with the primaryreceiver unit 104, as well as the data processing terminal 105. Thesecondary receiver unit 106 may be configured for bi-directionalwireless communication with each of the primary receiver unit 104 andthe data processing terminal 105. As discussed in further detail below,in certain embodiments the secondary receiver unit 106 may be ade-featured receiver as compared to the primary receiver, i.e., thesecondary receiver may include a limited or minimal number of functionsand features as compared with the primary receiver unit 104. As such,the secondary receiver unit 106 may include a smaller (in one or more,including all, dimensions), compact housing or embodied in a device suchas a wrist watch, arm band, etc., for example. Alternatively, thesecondary receiver unit 106 may be configured with the same orsubstantially similar functions and features as the primary receiverunit 104. The secondary receiver unit 106 may include a docking portionto be mated with a docking cradle unit for placement by, e.g., thebedside for night time monitoring, and/or bi-directional communicationdevice.

Only one sensor 101, data processing unit 102 and data processingterminal 105 are shown in the embodiment of the analyte monitoringsystem 100 illustrated in FIG. 1.

However, it will be appreciated by one of ordinary skill in the art thatthe analyte monitoring system 100 may include more than one sensor 101and/or more than one data processing unit 102, and/or more than one dataprocessing terminal 105. Multiple sensors may be positioned in a patientfor analyte monitoring at the same or different times. In certainembodiments, analyte information obtained by a first positioned sensormay be employed as a comparison to analyte information obtained by asecond sensor. This may be useful to confirm or validate analyteinformation obtained from one or both of the sensors. Such redundancymay be useful if analyte information is contemplated in criticaltherapy-related decisions. In certain embodiments, a first sensor may beused to calibrate a second sensor.

The analyte monitoring system 100 may be a continuous monitoring system,or semi-continuous, or a discrete monitoring system. In amulti-component environment, each component may be configured to beuniquely identified by one or more of the other components in the systemso that communication conflict may be readily resolved between thevarious components within the analyte monitoring system 100. Forexample, unique identification codes (IDs), communication channels, andthe like, may be used.

In certain embodiments, the sensor 101 is physically positioned in or onthe body of a user whose analyte level is being monitored. The sensor101 may be configured to at least periodically sample the analyte levelof the user and convert the sampled analyte level into a correspondingsignal for transmission by the data processing unit 102. The dataprocessing unit 102 is coupleable to the sensor 101 so that both devicesare positioned in or on the user's body, with at least a portion of theanalyte sensor 101 positioned transcutaneously. The data processing unit102 performs data processing functions, where such functions may includebut are not limited to, filtering and encoding of data signals, each ofwhich corresponds to a sampled analyte level of the user, fortransmission to the primary receiver unit 104 via the communication link103. In one embodiment, the sensor 101 or the data processing unit 102or a combined sensor/data processing unit may be wholly implantableunder the skin layer of the user.

In one aspect, the primary receiver unit 104 may include an analoginterface section including an RF receiver and an antenna that isconfigured to communicate with the data processing unit 102 via thecommunication link 103, data processing unit 102 and a data processingsection for processing the received data from the data processing unit102 such as data decoding, error detection and correction, data clockgeneration, and/or data bit recovery.

In operation, the primary receiver unit 104 in certain embodiments isconfigured to synchronize with the data processing unit 102 to uniquelyidentify the data processing unit 102, based on, for example, anidentification information of the data processing unit 102, andthereafter, to periodically receive signals transmitted from the dataprocessing unit 102 associated with the monitored analyte levelsdetected by the sensor 101.

Referring back to FIG. 1, each of the primary receiver unit 104 and thesecondary receiver unit 106 may include a blood glucose test strip portsuch that the user or the patient may perform finger prick tests usingblood glucose test strips. Accordingly, in aspects of the presentdisclosure, the primary receiver unit 104 and the secondary receiverunit 106 may incorporate the functionalities of a blood glucose meterfor processing a blood sample to determine a corresponding blood glucosemeasurement which may be performed by one or more controllers providedin the receiver unit including, for example, a microprocessor,application specific integrated circuit and/or a state machine forexecuting one or more routines associated with the processing anddetermination of blood glucose sample to determine the blood glucoselevel.

Exemplary analyte systems including calibration of analyte sensors thatmay be employed are described in, for example, U.S. Pat. Nos. 6,134,461,6,175,752, 6,121,611, 6,560,471, 6,746,582, 7,299,082 and in U.S. patentapplication Ser. No. 10/745,878 filed Dec. 26, 2003, now U.S. Pat. No.7,811,231, entitled “Continuous Glucose Monitoring System and Methods ofUse”, the disclosures of each of which are herein incorporated byreference.

Referring again to FIG. 1, the data processing terminal 105 may includea personal computer, a portable computer such as a laptop or a handhelddevice (e.g., personal digital assistants (PDAs), telephone such as acellular phone (e.g., a multimedia and Internet-enabled mobile phonesuch as an iPhone, Palm® device, Blackberry® device or similar device),mp3 player, pager, and the like), drug delivery device, each of whichmay be configured for data communication with the receiver via a wiredor a wireless connection. Additionally, the data processing terminal 105may further be connected to a data network (not shown) for additionallystoring, retrieving, updating, and/or analyzing data corresponding tothe detected analyte level of the user.

In certain embodiments, the communication link 103 as well as one ormore of the other communication interfaces shown in FIG. 1 tocommunicate data between the data processing unit 102, the primaryreceiver unit 104, secondary receiver unit 106 and the data processingterminal 105 may use one or more of an RF communication protocol, aninfrared communication protocol, a Bluetooth® enabled communicationprotocol, an 802.11x wireless communication protocol, or an equivalentwireless communication protocol which would allow secure, wirelesscommunication of several units (for example, per HIPAA requirements)while avoiding potential data collision and interference.

Furthermore, data communication between the primary receiver unit 104and the data processing terminal 105, or between the secondary receiverunit 106 and the data processing terminal 105 may include wireless orwired connection such as USB connection, RS-232 connection, serialconnection, and the like, to transfer data between the one or more ofthe primary and the secondary receiver units 104, 106 to the dataprocessing terminal 105.

FIG. 2 is an example flowchart for optimizing analyte sensor calibrationin accordance with one embodiment of the present disclosure. Referringto FIG. 2, in one aspect, when a blood glucose information is received(210) for example, using a finger prick test using a blood glucose teststrip, an analyte sensor calibration schedule associated with theanalyte sensor 101 (FIG. 1) is retrieved (220). In one aspect, thecalibration schedule may include a predetermined time interval at whichthe sensor 101 is calibrated using a reference measurement such as ablood glucose measurement. In one aspect, one or more memory module orstorage unit of the receiver unit 104/106 may store the calibrationschedule associated with the sensor 101.

Referring back to FIG. 2, with the retrieved analyte sensor calibrationschedule, a temporal proximity of the next upcoming scheduledcalibration event is determined (230). That is, in one aspect, when ablood glucose measurement is received, the sensor calibration scheduleis reviewed to determine when the next scheduled calibration event is tooccur. Thereafter, the temporal proximity is compared to a predeterminedtime period to determine whether the timing of when the current bloodglucose measurement is within a time window associated with the nextscheduled calibration event (240).

For example, given an exemplary calibration schedule of 10 hours, 12hours, 24 hours and 72 hours measured from the analyte sensorpositioning in the patient, when the reference blood glucose measurementis received at the 23^(rd) hour from when the sensor was positioned inthe patient, the temporal proximity is determined to be approximatelyone hour from the next scheduled calibration event (at the 24^(th)hour). The temporal proximity is then compared to the predetermined timeperiod which may be pre-programmed, for example, in the receiver unit(104/106) and may include, for example 90 minutes.

That is, in the example provided above, when a blood glucose measurementis received not in response to an execution of a calibration routine tocalibrate the sensor 101, it is determined whether the timing of thereceived blood glucose measurement is within the predetermined timeperiod from the next scheduled calibration event. Referring back to FIG.2, if it is determined that the temporal proximity of the upcoming ornext scheduled calibration event is within the predetermined timeperiod, then the calibration routine to calibrate the analyte sensor isinitiated (250).

In one embodiment, when the calibration routine is initiated, apreliminary check, the calibration conditions are evaluated to determineif calibration of the analyte sensor is appropriate, and when it isdetermined that the calibration conditions are appropriate, the routineproceeds with executing one or more functions associated with thecalibration of the analyte sensor. Moreover, as part of the calibrationroutine, when initiated, the current blood glucose information as wellas other data or information may be stored in a memory or storage unitof the receiver unit 104/106.

Referring back to FIG. 2, on the other hand, if it is determined thatthe temporal proximity is not within the predetermined time period(240), the current blood glucose measurement received is stored, forexample, in a memory or storage unit of the receiver unit 104/106 (260).Additionally, the user or the patient may be notified of the successfulcalibration event, and further, that the successful calibration eventoverrides the upcoming scheduled calibration, and that the user or thepatient will not be prompted or requested to perform the upcomingscheduled calibration including providing another blood glucoseinformation.

In this manner, in one aspect, when the patient or the user of theanalyte monitoring system 100 (FIG. 1) performs a blood glucosemeasurement between the scheduled calibration time periods, adetermination is made to accept the blood glucose measurement to performcalibration of the analyte sensor 101. Thereafter, the upcoming or nextscheduled calibration event may be overridden or updated with thecalibration performed based on the blood glucose measurement received.

Accordingly, additional flexibility and robustness may be provided inthe analyte monitoring system 100 while minimizing the number of bloodglucose measurements to calibrate the analyte sensor 101 during itsuseful life. In other words, when the patient or the user of the analytemonitoring system 100 performs a self-initiated blood glucosemeasurement (for example, using a standard blood glucose meter, or usingthe receiver unit 104/106 having such functionality integrated therein),in one aspect, it is determined whether the blood glucose measurementmay be used to perform calibration of the analyte sensor, and in whichcase, the next scheduled calibration event may be overridden or notperformed as the conditions are such that the calibration routine usingthe received current blood glucose measurement may replace the upcomingscheduled calibration event.

By way of an example, there may be circumstances where patient motivatedblood glucose measurements are performed sufficiently close to the nextscheduled calibration of the analyte sensor 101 such that the nextscheduled calibration event may be replaced with the calibration routineperformed based on the patient motivated blood glucose measurements.Accordingly, in one aspect, the patient or the user of the analytemonitoring system 100 may be subject to one less finger prick test todetermine blood glucose measurement to calibrate the analyte sensor 101.

While particular examples are provided above for the predetermined timeperiod used to compare the temporal proximity of the current bloodglucose measurement to the next or upcoming scheduled calibration event,and further, while particular example calibration schedule is describedabove, within the scope of the present disclosure, the particularpredetermined time period to compare the temporal proximity of the bloodglucose measurement, or the particular calibration schedule may bevaried. For example, the calibration schedule may be provided to requirecalibration routine once every 24 hours measured from the initial sensorinsertion. Alternatively, the calibration schedule time periods may bedifferent for each period during the life of the sensor (which may be 3days, 5 days, 7 days or more), and further, each subsequent calibrationroutine after the initial calibration may be determined relative to theimmediately preceding successful calibration routine performed, and notrelative to the time associated with the initial sensor insertion.Moreover, the predetermined time period used to compare the temporalproximity may include other time periods such as approximately one hour,or approximately two hours, or any other suitable time period ratherthan approximately 90 minutes.

FIG. 3 is an example flowchart for optimizing analyte sensor calibrationin accordance with another embodiment of the present disclosure.Referring to FIG. 3, in a further aspect, after receiving calibrationreference data (310), temporal proximity of the next scheduled analytesensor calibration event is determined (320). Thereafter, the determinedtemporal proximity is compared to a predetermined time period asdescribed above (330), and when it is determined that the temporalproximity is not within the predetermined time period, the receivedcalibration reference data is stored (370) and the routine terminates.

On the other hand, referring back to FIG. 3, when it is determined thatthe temporal proximity of the next scheduled analyte sensor calibrationevent is within the predetermined time period (relative to when thecalibration reference data is received, for example), a request toconfirm analyte sensor calibration may be generated and provided to theuser or the patient (340). In this manner, the user or the patient maybe provided with an opportunity to accept or decline the execution ofthe calibration routine based on the calibration reference data giventhe temporal proximity of the next or subsequent upcoming calibrationschedule to calibrate the analyte sensor 101 (FIG. 1).

In one aspect, using an output device such as a display on the receiverunit 104/106, the user may be prompted to confirm the execution of thecalibration routine in addition to providing information associated withwhen the next scheduled calibration is to occur. Referring yet again toFIG. 3, when user confirmation acknowledgement is not received (350),then the calibration reference data is stored (370) and the routineterminates. On the other hand, if the user confirmation acknowledgementis received (350), then the analyte sensor calibration routine isinitiated (360) to execute the routine associated with the calibrationof the analyte sensor. As discussed above, as part of the initiatedcalibration routine, the calibration reference data as well as otherinformation and data may be stored in the memory or storage device ofthe receiver unit 104/106.

Referring back to FIG. 3, in a further aspect, when it is determinedthat the temporal proximity of the next scheduled analyte sensorcalibration event is within the predetermined time period, prior tosending the request to confirm the calibration event, calibrationconditions may be evaluated to determine whether analyte sensorcalibration conditions are appropriate. Alternatively, evaluation of thecalibration conditions may be performed after the user or the patienthas provided acknowledgement confirmation to perform the calibration.

As discussed in further detail below, initiating the calibration routinemay include, in one aspect, validating or confirming the acceptabilityof the received calibration reference data (for example, a determinationthat the blood glucose measurement used as the calibration referencedata is within a predefined acceptable range such as 40 mg/dL to 400mg/dL). Additionally, conditions or parameters associated with theexecution of the calibration routine may be performed including, forexample, determining the rate of the change of the analyte level to bewithin an acceptable range for calibration, the temperature informationassociated with the analyte sensor is within an acceptable range, orthere are a sufficient number of analyte sensor data points to performcalibration.

FIG. 4 is an example flowchart for optimizing analyte sensor calibrationin accordance with yet another embodiment of the present disclosure.Referring to FIG. 4, in one aspect, when the current reference data isreceived (410), temporal proximity of the next scheduled analyte sensorcalibration event is confirmed to be within a predetermined time period(for example, such as 90 minutes from when the current reference data isreceived) (420). Thereafter, calibration conditions are validated todetermine that conditions associated with the patient and the analytesensor, among others, are appropriate (430).

For example, in one aspect, the calibration condition may not be validwhen the rate of change of the analyte level exceeds a predeterminedthreshold level or range. In another aspect, the calibration conditionmay be determined to be invalid when insufficient analyte sensor datapoints are present (whether due to data packet drop outs from the dataprocessing unit 102 (FIG. 1), or signal dropout events such as signalattenuation. Within the scope of the present disclosure, otherparameters and/or conditions are reviewed and analyzed to determinewhether the calibration condition is valid. Examples of such otherparameters or conditions are further described in U.S. Pat. Nos.6,175,752 and 7,299,083, among others, the disclosure of each of whichare incorporated by reference for all purposes.

Referring back to FIG. 4, upon validation of the calibration conditions(430), the analyte sensor is calibrated using the received currentreference data (440). Moreover, after calibration, the storedcalibration schedule in one aspect may be retrieved and updated toinclude the calibration performed based on the received currentreference data (450). Moreover, in one aspect, the retrieved calibrationschedule may be updated to replace the next scheduled analyte sensorcalibration event with the calibration based on the current referencedata.

In the manner provided, within the scope of the present disclosure,using the non-calibration prompted and user initiated blood glucosemeasurements, under certain conditions such as time proximity to thesubsequent scheduled calibration event, among others, the number ofrequired blood glucose measurement using a blood glucose test strip maybe minimized.

Referring still to the various embodiments of the present disclosure, asdiscussed above, the analyte monitoring system may automatically performthe calibration of the analyte sensor based on the blood glucosemeasurement received, and thereafter, notify the user or the patient ofthe successful calibration of the sensor, or alternatively, provide thepatient or the user with the option to confirm the performance of thecalibration of the sensor based on the receive blood glucosemeasurement. Within the scope of the present disclosure, othervariations or levels of user or patient interaction may be contemplated,such as, for example, notification (alarms or alerts that are visual,auditory, vibratory or one or more combinations thereof) to the user ofcalibration associated events such as updating the previously storedcalibration schedule based on the calibration performed with the currentreference or blood glucose data, notification of the next validscheduled calibration, the number of calibrations remaining for thesensor prior to sensor replacement, failed calibration attempt,unsuitable calibration conditions, verified valid calibrationconditions, and the like.

Accordingly, a method in one aspect includes receiving a current bloodglucose measurement, retrieving a time information for an upcomingscheduled calibration event for calibrating an analyte sensor,determining temporal proximity between the current blood glucosemeasurement and the retrieved time information for the upcomingcalibration event, and initiating a calibration routine to calibrate theanalyte sensor when the determined temporal proximity is within apredetermined time period.

In one aspect, initiating the calibration routine may includecalibrating the analyte sensor based on the received current bloodglucose measurement.

Moreover, the method may include determining validity of the currentblood glucose measurement, for example, by comparing the current bloodglucose measurement to predetermined ranges or values.

Additionally, determining validity of the current blood glucosemeasurement may include analyzing the current blood glucose measurementbased on a predetermined threshold range, a temperature information, ora combination thereof.

In still another aspect, the method may include determining the validityof an analyte sensor data, including one or more of analyzing theanalyte sensor data based on one or more of a rate of change of theanalyte level, a temperature information, a predetermined analyte levelthreshold range, or one or more combinations thereof.

In another aspect, the method may include overriding the upcomingscheduled calibration event when the calibration routine to calibratethe analyte sensor based on the received current blood glucosemeasurement is successful.

Also, initiating the calibration routine may include validating one ormore calibration condition parameters associated with the calibration ofthe analyte sensor.

Yet still further aspect may include generating an output signalconfirming completion of the upcoming scheduled calibration event.

In yet another aspect, the method may include updating a calibrationschedule for calibrating the analyte sensor based on the initiatedcalibration routine.

Further, initiating calibration routine may include automaticallyperforming the calibration routine to calibrate the analyte sensor whenthe determined temporal proximity is within the predetermined timeperiod.

A method in accordance with another aspect of the present disclosureincludes receiving a current reference data associated with a monitoredanalyte level, determining whether a next scheduled calibration eventfor calibrating an analyte sensor associated with the monitored analytelevel is within a predetermined time period, validating one or moreconditions associated with the calibration of the analyte sensor whenthe next scheduled calibration event is determined to be within thepredetermined time period, and calibrating the analyte sensor based onthe received current reference data.

The analyte sensor may be associated with a time spaced calibrationschedule including the next scheduled calibration event.

The time spaced calibration schedule may include an unevenly time spacedcalibration schedule during the life of the sensor.

In another aspect, the method may include updating the time spacedcalibration schedule based on analyte sensor calibration using thereceived current reference data

Also, the method may include associating the current reference data witha corresponding calibrated analyte sensor data.

Additionally, in a further aspect, the method may include disabling acalibration routine associated with the next scheduled calibrationevent.

An apparatus in accordance with another aspect of the present disclosureincludes one or more processors, and a memory operatively coupled to theone or more processors for storing instructions which, when executed bythe one or more processors, retrieves a time information for an upcomingscheduled calibration event for calibrating an analyte sensor when acurrent blood glucose measurement is received, determines a temporalproximity between the current blood glucose measurement and theretrieved time information for the upcoming calibration event, andinitiates a calibration routine to calibrate the analyte sensor when thedetermined temporal proximity is within a predetermined time period.

The apparatus may include a blood glucose strip port configured toreceive a blood glucose test strip providing the current blood glucosemeasurement. That is, in one aspect, the receiver unit 104/106 (FIG. 1)may include an integrated blood glucose test strip port and beconfigured to analyze the blood sample received from the test strip todetermine the corresponding blood glucose level.

In still another aspect, the apparatus may include a housing coupled tothe blood glucose strip port and further, wherein the one or moreprocessors and the memory are provided in the housing.

The various processes described above including the processes performedby the one or more processors of the receiver unit 104/106, oroptionally the data processing unit 102 (FIG. 1), in the softwareapplication execution environment as well as any other suitable orsimilar processing units embodied in the analyte monitoring system 100,including the processes and routines described in conjunction with FIGS.2-4, may be embodied as computer programs developed using an objectoriented language that allows the modeling of complex systems withmodular objects to create abstractions that are representative of realworld, physical objects and their interrelationships. The softwarerequired to carry out the inventive process, which may be stored in amemory (or similar storage devices in the data processing unit 102, orthe receiver unit 104/106) of the processor, may be developed by aperson of ordinary skill in the art and may include one or more computerprogram products.

Various other modifications and alterations in the structure and methodof operation of this present disclosure will be apparent to thoseskilled in the art without departing from the scope and spirit of thepresent disclosure. Although the present disclosure has been describedin connection with specific preferred embodiments, it should beunderstood that the present disclosure as claimed should not be undulylimited to such specific embodiments. It is intended that the followingclaims define the scope of the present disclosure and that structuresand methods within the scope of these claims and their equivalents becovered thereby.

What is claimed is: 1) A continuous glucose monitoring system,comprising: a transcutaneous glucose sensor having an in vivo portionconfigured to be positioned in contact with an interstitial fluid of auser; a data processing unit couplable to the transcutaneous glucosesensor and including a data processing unit non-transitory memory, andat least one data processing unit processor coupled to the dataprocessing unit non-transitory memory; and a receiver commutativelycoupled to the data processing unit via a communication link andincluding a receiver non-transitory memory, at least one receiverprocessor coupled to the receiver non-transitory memory; wherein atleast one of the at least one data processing unit processor and atleast one receiver processor is configured to store a calibrationschedule in the respective non-transitory memory, wherein thecalibration schedule comprises a plurality of scheduled calibrationevents for receiving scheduled blood glucose measurements to calibratethe glucose sensor; upon receiving an unscheduled blood glucosemeasurement after a successful prior scheduled calibration event, butbefore a next scheduled calibration event, at least one of the at leastone data processing unit processor and the at least one receiverprocessor is configured to provide a prompt to verify the unscheduledblood glucose measurement; upon receiving a confirmation acknowledgmentto the prompt to verify the unscheduled blood glucose measurement, atleast one of the at least one data processing unit processor and the atleast one receiver processor is configured to perform an unscheduledcalibration event using the unscheduled blood glucose measurement tocalibrate the glucose sensor using the unscheduled blood glucosemeasurement; at least one of the at least one data processing unitprocessor and the at least one receiver processor is configured todetermine if the unscheduled calibration event successfully calibratedthe glucose sensor; at least one of the at least one data processingunit processor and the at least one receiver processor is configured toprovide a notification if the unscheduled calibration event failed; andat least one of the at least one data processing unit processor and theat least one receiver processor is configured to update the calibrationschedule to override or modify the next scheduled calibration event ifthe unscheduled calibration event was successful. 2) The system of claim1, wherein to update the calibration schedule, at least one of the atleast one data processing unit processor and the at least one receiverprocessor is further configured to modify the next scheduled calibrationevent to be a fixed time period after the unscheduled calibration event.3) The system of claim 2, wherein the fixed time period is the same as atime period between the successful prior scheduled calibration event andthe next scheduled calibration event before modification of the nextcalibration event. 4) The system of claim 1, wherein to perform theunscheduled calibration event, at least one of the at least one dataprocessing unit processor and the at least one receiver processor isfurther configured to validate a calibration condition parameterassociated with the calibration of the glucose sensor. 5) The system ofclaim 4, wherein to validate the calibration condition parameterassociated with the calibration of the glucose sensor, at least one ofthe at least one data processing unit processor and the at least onereceiver processor is further configured to determine if the unscheduledblood glucose measurement is within an acceptable range. 6) The systemof claim 4, wherein the calibration condition parameter comprises aglucose rate of change. 7) The system of claim 1, wherein thecalibration schedule comprises a first predetermined calibration eventscheduled 12 hours after a prior scheduled calibration event. 8) Thesystem of claim 7, wherein the calibration schedule comprises a secondpredetermined calibration event scheduled 12 hours after the firstscheduled predetermined calibration event. 9) The system of claim 8,wherein the calibration schedule comprises a third predeterminedcalibration event scheduled 24 hours after the second scheduledpredetermined calibration event. 10) The system of claim 9, wherein thecalibration schedule comprises additional predetermined calibrationevents scheduled every 24 hours after the third scheduled predeterminedcalibration event 11) The system of claim 7, wherein upon receiving theunscheduled blood glucose measurement after the first predeterminedcalibration event and before the second predetermined calibration event,at least one of the at least one data processing unit processor and theat least one receiver processor is further configured to update thecalibration schedule by modifying the second predetermined calibrationevent to be scheduled 12 hours after the unscheduled calibration event.12) The system of claim 8, wherein upon receiving the unscheduled bloodglucose measurement after the first predetermined calibration event andbefore the second predetermined calibration event, at least one of theat least one data processing unit processor and the at least onereceiver processor is further configured to update the calibrationschedule by modifying the second predetermined calibration event to bescheduled 12 hours after the unscheduled calibration event and the thirdpredetermined calibration event to be scheduled 24 hours after themodified second predetermined calibration event. 13) The system of claim9, wherein upon receiving the unscheduled blood glucose measurementafter the first predetermined calibration event and before the secondpredetermined calibration event, at least one of the at least one dataprocessing unit processor and the at least one receiver processor isfurther configured to update the calibration schedule by modifying thesecond predetermined calibration event to be scheduled 12 hours afterthe unscheduled calibration event, the third predetermined calibrationevent to be scheduled 24 hours after the modified second predeterminedcalibration event, and the additional predetermined calibration eventsto be scheduled every 24 hours after the modified third scheduledpredetermined calibration event. 14) The system of claim 9, wherein uponreceiving the unscheduled blood glucose measurement after the secondpredetermined calibration event and before the third predeterminedcalibration event, at least one of the at least one data processing unitprocessor and the at least one receiver processor is further configuredto update the calibration schedule by modifying the third predeterminedcalibration event to be scheduled 24 hours after the unscheduledcalibration event. 15) The system of claim 10, wherein upon receivingthe unscheduled blood glucose measurement after the second predeterminedcalibration event and before the third predetermined calibration event,at least one of the at least one data processing unit processor and theat least one receiver processor is further configured to update thecalibration schedule by modifying the third predetermined calibrationevent to be scheduled 24 hours after the unscheduled calibration eventand the additional predetermined calibration events to be scheduledevery 24 hours after the modified third scheduled predeterminedcalibration event. 16) The system of claim 1, wherein the calibrationschedule comprises a first predetermined calibration event scheduled 24hours after a prior scheduled calibration event. 17) The system of claim16, wherein the calibration schedule comprises a second predeterminedcalibration event scheduled 24 hours after the first scheduledpredetermined calibration event. 18) The system of claim 17, wherein thecalibration schedule comprises additional predetermined calibrationevents scheduled every 24 hours after the second scheduled predeterminedcalibration event. 19) The system of claim 17, wherein upon receivingthe unscheduled blood glucose measurement after the first predeterminedcalibration event and before the second predetermined calibration event,at least one of the at least one data processing unit processor and theat least one receiver processor is further configured to update thecalibration schedule by modifying the second predetermined calibrationevent to be scheduled 24 hours after the unscheduled calibration event.20) The system of claim 18, wherein upon receiving the unscheduled bloodglucose measurement after the first predetermined calibration event andbefore the second predetermined calibration event, at least one of theat least one data processing unit processor and the at least onereceiver processor is further configured to update the calibrationschedule by modifying the second predetermined calibration event to bescheduled 24 hours after the unscheduled calibration event and theadditional predetermined calibration events to be scheduled every 24hours after the modified second scheduled predetermined calibrationevent. 21) The system of claim 1, wherein the calibration schedulecomprises a plurality of different time periods between the plurality ofscheduled calibration events. 22) The system of claim 1, wherein atleast one of the at least one data processing unit processor and the atleast one receiver processor is further configured to determine avalidity of glucose sensor data from the glucose sensor. 23) The systemof claim 1, wherein the unscheduled blood glucose measurement isdetermined via a blood glucose test strip. 24) The system of claim 1,wherein to calibrate the glucose sensor using the unscheduled bloodglucose measurement, at least one of the at least one data processingunit processor and the at least one receiver processor is furtherconfigured to: change a parameter associated with the glucose sensorbased on the unscheduled blood glucose measurement. 25) One or morecomputer-readable non-transitory storage media embodying software thatis operable when executed to: store a calibration schedule in thenon-transitory memory, wherein the calibration schedule comprises aplurality of scheduled calibration events for receiving scheduled bloodglucose measurements to calibrate a glucose sensor; upon receiving anunscheduled blood glucose measurement after a successful prior scheduledcalibration event but before a next scheduled calibration event, providea prompt to verify the unscheduled blood glucose measurement; uponreceiving a confirmation acknowledgment to the prompt to verify theunscheduled blood glucose measurement, perform an unscheduledcalibration event using the unscheduled blood glucose measurement tocalibrate the glucose sensor using the unscheduled blood glucosemeasurement; determine if the unscheduled calibration event successfullycalibrated the glucose sensor; provide a notification if the unscheduledcalibration event failed; and update the calibration schedule tooverride or modify the next scheduled calibration event if theunscheduled calibration event was successful. 26) The media of claim 25,wherein the updating the calibration schedule further comprisesmodifying the next scheduled calibration event to be a fixed time periodafter the unscheduled calibration event. 27) The media of claim 26,wherein the fixed time period is the same as a time period between thesuccessful prior scheduled calibration event and the next scheduledcalibration event before modification. 28) The media of claim 27,wherein performing the unscheduled calibration event further comprisesvalidating a calibration condition parameter associated with thecalibration of the glucose sensor. 29) The media of claim 28, whereinthe validating further comprises determining if the unscheduled bloodglucose measurement is within an acceptable range. 30) The media ofclaim 28, wherein the calibration condition parameter comprises aglucose rate of change.